An Activatable Near-Infrared Chromophore for Multispectral Optoacoustic Imaging of Tumor Hypoxia and for Tumor Inhibition

摘要

Hypoxia is a key hallmark of solid tumors and tumor hypoxia usually contributes to cancer progression, therapeutic resistance and poor outcome. Accurately detecting and imaging tumor hypoxia with high spatial resolution would be conducive to formulating optimized treatment plan and thus achieving better patient outcome. Methods : Tumor hypoxia can cleave the azo linker and release a NIR fluorophore (NR-NHsub2/sub) and release the active drug as well. NR-NHsub2/sub shows a strong absorption band at around 680 nm and a strong fluorescence band at 710 nm, allowing for both multispectral optoacoustic tomography imaging (MSOT) and fluorescent imaging of tumor hypoxia in a tumor-bearing mouse model. Results : Liposome encapsulated with the activatable chromophore (NR-azo) for detecting/imaging tumor hypoxia and for tumor inhibition was demonstrated. For this chromophore, a xanthene-based NIR fluorophore acts as the optoacoustic and fluorescent reporter, an azo linker serves as the hypoxia-responsive moiety and a nitrogen mustard as the therapeutic drug. NR-azo shows an absorption at around 575 nm but exhibits negligible fluorescence due to the existence of the strong electron-withdrawing azo linker. Conclusion : We demonstrated an optoacoustic and fluorescent system for not only imaging tumor hypoxia in vivo but also achieving tumor inhibition.